Abstension from treatment of low-level pp65 cytomegalovirus antigenemia after liver transplantation: a prospective study

BACKGROUND: Ganciclovir is a highly effective and relatively safe drug to treat cytomegalovirus (CMV) infection in liver transplant patients; CMV resistance to ganciclovir is progressively emerging due to the extensive use of the drug in transplant and AIDS patients; CMV pp65 antigenemia allows early diagnosis of CMV infection and quantitation of the viral load; preemptive antigenemia-guided therapy of CMV infection can prevent CMV disease but the threshold of antigenemia value above which treatment has to be instituted is unclear. METHODS: To demonstrate the safety of abstention from preemptive treatment in the presence of low levels of antigenemia 77 consecutive liver transplant recipients were prospectively evaluated. Antigenemia was tested twice a week from transplantation until discharge, then once a week until the third postoperative month. In absence of risk factors for CMV disease, namely donor positive/recipient negative CMV serology, treatment with antibodies to lymphocytes and retransplantation, only patients with antigenemia of more than 50 or symptoms possibly related to CMV infection had preemptive treatment. RESULTS: A total of 32 patients had at least one positive antigenemia test with a value less than 50; 22 (68.7%) spontaneously cleared the virus, 3 were treated with i.v. ganciclovir for the presence of fever, and the other 7 (21,8%) progressed to values of antigenemia of more than 50 and were treated even if asymptomatic. No CMV disease was observed in these patients. CONCLUSION: CMV antigenemia less than 50 in liver transplant recipients with low and intermediate risk for CMV disease does not mandate preemptive ganciclovir treatment. Close surveillance with repeated determination of antigenemia until its negativization and careful clinical and laboratory monitoring is advisable.     

The Risk Factors for Cytomegalovirus Syndrome and Tissue-invasive Cytomegalovirus Disease in Liver Transplant Recipients Who Have Cytomegalovirus Antigenemia

Cytomegalovirus (CMV) infection is not only a common complication after liver transplantation (OLT), but also a significant contributing factor to morbidity and mortality. We investigated risk factors for CMV syndrome and tissue-invasive CMV disease in CMV antigenemia patients after OLT in a CMV endemic area. CMV antigenemia was regarded to be >1 positive CMV pp65 antigen positive cell per 400,000 white blood cells. We examined the epidemiology, clinical characteristics, and laboratory findings of liver transplant patients with CMV syndrome and tissue-invasive CMV disease. The incidence of CMV syndrome among patients with CMV antigenemia was 10.5% (37/353) and that of tissue-invasive CMV disease, 3.1% (11/353). Upon multivariate analysis the risk factors for CMV syndrome and tissue-invasive CMV disease were infection, low albumin level, high total bilirubin content, and high CMV peak titer. The 1-y, 2-y, and 3-year survival rates of subjects without CMV syndrome were 96.2%, 85.4% and 82.2% versus without tissue-invasive CMV disease, 86.9%, 83.0%, and 80.1%, or 70.3%, 56.1% and 51.8% for CMV syndrome or 72.7%, 62.3%, 49.9% for tissue-invasive CMV disease. The survival curve of patients without were superior to those with CMV syndrome (P = .000). Because OLT recipients had risk factors such as infection, low albumin level, high total bilirubin content, and high CMV peak titer, they were carefully monitored and aggressively managed due to the poor survivals of patients with CMV syndrome.     

Risk Factors for Posttransplant Lymphoproliferative Disorder in Pediatric Liver Transplant Recipients With Cytomegalovirus Antigenemia

Epstein-Barr virus (EBV) infections, associated with posttransplant lymphoproliferative disorder (PTLD) are known to develop in cytomegalovirus (CMV)-infected transplant recipients due to the indirect effects of CMV. This study evaluated risk factors for PTLD among pediatric liver transplant recipients with CMV infections. We reviewed the medical records of 119 patients ≤18 years old who underwent liver transplantation between September 1996 and April 2009. Sixty-six subjects (55.5%) displayed CMV antigenemia during the study period; 15 (12.6%) developed PTLD. Of these, 10 developed PTLD after CMV antigenemia. The other patients (n = 5) were excluded due to negative CMV antigenemia. The incidence of PTLD influenced by CMV infection was not significantly different from the incidence of PTLD without underlying CMV (P = .258). There were no differences in age, gender, antiviral prophylaxis, type of liver transplantation, or acute rejection episodes in the incidence of between patients with versus without PTLD. EBV but not CMV high-risk groups were a predictor for the development of PTLD (P = .035). CMV syndrome, tissue-invasive CMV disease, and CMV peak titer were not associated with an increased risk of PTLD. The primary risk factor for PTLD was EBV high-risk patients (donor positive/recipient negative). CMV disease was not associated with PTLD in pediatric liver transplant recipients with CMV infections.     

Risk factors associated with cytomegalovirus infection in orthotopic liver transplant patients

Our objective was to investigate the potential risk factors associated with cytomegalovirus (CMV) infection. PATIENTS AND METHODS: From January 1999 to December 2001, 163 liver transplantations were performed in 154 patients. The study inclusion criteria were absence of retransplantation and survival of more than 6 months. One hundred fifteen patients met the inclusion criteria. We determined variables such as age, gender, and number of hemecomponents as well as serum IgG CMV status of donors and recipients. We recorded the immunosuppression used by each patient. CMV infection was detected by positive antigenemia. RESULTS: Recipient mean age was 50 years. The etiology of cirrhosis was viral (n = 57; 49.6%), alcoholic (n = 20; 17.4%), virus and alcohol (n = 15; 13.0%), cryptogenic (n = 14; 12.2%), or other causes (n = 9; 7.8%). CMV infection was positive in 75 patients (65.8%). There was no relation between infection and age, gender, or CMV IgG donor recipient status, or the number of hemecomponent units. The risk was 3.8-fold higher for patients receiving a three-drug compared with a two-drug regimen. When cyclosporine was used instead of tacrolimus, the risk of CMV infection was 4.3-fold higher. Logistic regression analysis revealed cyclosporine (OD=5.8) and a three-drug regimen (OD=6.7) to have stronger associations with CMV infection. CONCLUSION: The use of cyclosporine (OD=5.8) and a three-drug regimen (OD=6.7) are risk factors for CMV infection.     

肝移植术后巨细胞病毒再感染的预防与治疗

目的　探讨肝移植术后巨细胞病毒(CMV)再感染的预防、诊断及治疗。方法　回顾性分析44例原位肝移植患者的临床资料。结果　44 例中,术前43 例(97.7 %)有CMV潜伏性感染,其中6例(14.0 %)术后发生CMV再感染。6例CMV再感染患者的CMV pp65抗原均为阳性,3例CMV IgM阳性,均为无临床症状的CMV活动性感染,其中5例治愈,无一例发展为CMV病,1 例因上消化道大出血死亡。43例中,仅有7例CMV再感染高危病例接受了抗CMV感染的预防性治疗,患者在生存期内未发生CMV再感染。结论　在我国,肝移植患者术前CMV潜伏性感染的发生率较高,测定CMV pp65抗原可以早期诊断CMV再感染;对CMV再感染的高危患者进行预防性治疗可以降低术后CMV再感染的发生率;对无临床症状的CMV再感染者进行及时、规范的治疗是防止CMV病发生的关键。     

Cytomegalovirus infection and development of biliary complications after liver transplantation

BACKGROUND: Cytomegalovirus (CMV) infection is known to cause ulceration and mucosal hemorrhage in the gastrointestinal tract. Gastroduodenal and biliary complications were prospectively evaluated in 100 consecutive liver transplant patients in whom CMV was monitored during the first posttransplant year. METHOD: Gastroduodenal biopsy specimens were taken from 36 patients by endoscopies and in 28 patients by endoscopic retrograde cholangiopancreatography, and bile duct specimens were taken from three patients who underwent surgical reconstruction because of biliary complication. CMV was demonstrated from blood by the pp65 antigenemia test and from frozen sections of tissue specimens by immunohistochemistry and in situ hybridization. RESULTS: Symptomatic CMV infection, treated with ganciclovir, developed in 49 recipients: 13 (100%) of CMV seropositive donor (D+) seronegative recipient (R-) cases, 29 (45%) D+/R+ cases, and 7 (32%) D-/R+ cases. Duodenal ulcer developed in three and hemorrhagic gastritis in three recipients. CMV antigens were found from the gastroduodenal mucosa in 37 (69%) of the 54 studied recipients. The biliary complication rate was 24%. Preceding or concomitant CMV antigenemia was demonstrated in 75% of patients with a biliary complication (68% in CMV D+/R+ or D-/R+ and 100% in D+/R- recipients). The biliary complication rate was higher among recipients with CMV antigenemia, compared with recipients without (P<0.05). CMV antigenemia, CMV infection, or both in the duodenal mucosa was found in 96% of patients with a biliary complication. In two patients who underwent surgical reconstruction, CMV antigens and DNA were demonstrated in the bile ducts. CONCLUSIONS: Liver transplant patients are at risk of developing biliary complications after CMV infection, especially those with primary CMV infection.     

Cytomegalovirus infection of the upper gastrointestinal tract following liver transplantation--incidence, location, and severity in cyclosporine- and FK506-treated patients.

One hundred and forty randomly selected liver transplant recipients were studied before and after primary orthotopic liver transplantation for the presence or absence of CMV enteritis. Following OLTx, 65 patients were treated with cyclosporine A and 75 were treated with FK506. The two groups were similar with regard to the incidence, location, and outcome of their upper gastrointestinal CMV infection. Prior to OLTx, only one patient had evidence of enteric CMV infection. The incidence of CMV enteritis post-OLTx was 27.7% in the CsA-treated group and 20% in the FK-treated group. During the first posttransplant month, no patient in the FK-treated group developed CMV enteritis, compared with 11.5% of the patients who were treated with CsA (P less than 0.05). Gastric CMV was found in over 80% of those positive for any organ in either group. In addition to CMV infection of the upper gastrointestinal tract, clinically evident CMV disease involved more nonenteric organs in the CsA-treated group than in the FK-treated group. In the CsA-treated group, CMV-negative patients had a statistically higher 1-year survival rate (100%) than CMV-positive patients (77.8%) (P less than 0.05). In the FK-treated group, no difference in survival was observed between CMV-positive or CMV-negative cases at 1 year. Of the patients on CsA, 20% received OKT3 for persistent rejection, as compared with 13% in the FK-treated group. The patients receiving both CsA and OKT3 had a higher rate of upper gastrointestinal CMV infection than did FK-treated patients who also received OKT3 therapy (38.5% versus 20%, respectively). Based upon these data, it can be concluded that (1) patients receiving FK have a lower incidence of enteric CMV infection; (2) following OLTx, upper gastrointestinal CMV infection presents later in FK-treated patients; (3) the stomach is the most frequently involved organ in the UGIT; (4) FK-treated liver recipients have less severe enteric CMV infection than do CsA-treated patients; (5) enteric CMV is not a major cause of mortality in liver transplant recipients; and (6) in patients receiving FK, those who require OKT3 therapy do not appear to be at a greater risk for the development of CMV enteritis than those who do not.     

Acyclovir plus CMV immunoglobulin prophylaxis and early therapy with ganciclovir are effective and safe in CMV high-risk renal transplant pediatric recipients

Cytomegalovirus (CMV) infection is still a major cause of morbidity in high-risk renal transplant recipients. In the present report, we have reviewed our records of renal transplant pediatric recipients (RTPR; mean age 14.1 ± 4.9 years) since 1991, when we started a policy of CMV prophylaxis constituting high-dose oral acyclovir plus CMV hyperimmune immunoglobulins (Hlg) followed by early i. v. ganciclovir therapy in high-risk patients (i. e., CMV donor + / recipient ?). Four patients received a kidney from a living relative (LR), 2 patients had one previous transplant, and 1 had a combined liver – kidney transplant. Thirty-three patients who were negative for CMV antibodies (ab) before transplantation received a kidney from CMV ab positive donors. The immunosuppressive regimen included cyclosporine A and steroids, with the addition of azathioprine in the 4 patients who received an LR kidney. Serial assessments for CMV antigenemia (pp 65) were routinely performed for 6 months after transplantation to define CMV infection. Among the 33 CMV seronegative recipients (R ?) who received the graft from a CMV seropositive donor (D +), 18 (54.5 %) experienced CMV infection, whereas among the 28 CMV R +, who received a graft from a CMV D +, 11 (39.3 %) experienced CMV infection. With regard to CMV ? related symptoms, only 2 patients suffered from a CMV syndrome (fever and leukopenia in 1 patient, fever and arthralgia in the other). In no case did the spectrum of CMV disease occur; only minor symptoms were present in 7 of the remaining CMV-infected patients (fever in 6 and leukopenia in 1). Rejection episodes and renal function did not differ between CMV-infected and non-CMV-infected patients. Our experiences support the use of prophylactic acyclovir plus CMV HIg followed by early therapy with i. v. ganciclovir to combat the risk of increased morbidity in high risk RTPR.     

Experience with low-dose valganciclovir prophylaxis in adult liver transplant recipients

Valganciclovir (VGCV) is considered the agent of choice after organ transplant for cytomegalovirus (CMV) prophylaxis. The purpose of this retrospective study was to determine the effectiveness and safety of a low-dose regimen after liver transplant (OLT). Eighty-five patients who underwent OLT between August 2002 and August 2004 were included. All patient data for the first 12 months after transplant were collected. Patients received VGCV 450 mg once daily for 3 months posttransplant. CMV infection was based on detection of CMV virus or viral proteins in blood. CMV disease was defined by the presence of positive antigenemia/viremia and evidence of clinical symptoms and/or tissue findings. Patients were D+R+ (54%) and D-R+ (29%), D+R-(11%) and D-R-(6%). Overall, CMV infection and disease occurred in 13% (11/85). CMV infection and disease occurred in 7% and 6%, respectively. CMV infection and disease occurred in 44% (D+R-), 13% (D+R+), 4% (D-R+) patients. The mean time to onset of CMV infection and disease was 103 days (14 to 312 days). Overall, 82% of patients received antibody therapy. The most common adverse events associated with VGCV were leukopenia (16%), thrombocytopenia (4%), anemia (<1%), and neurotoxicity (<1%). Low-dose VGCV was not an effective means to prevent CMV infection in high-risk (D+R-) patients, especially those who received antibody induction. High-risk patients may require a high-dose regimen, such as 900 mg daily, and/or a longer period of prophylaxis, and/or reduction in the use of potent antibody treatments after liver transplant.     

Cytomegalovirus antigenemia directed pre-emptive prophylaxis with oral versus I.V. ganciclovir for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, controlled trial

BACKGROUND: The efficacy of pre-emptively administered oral ganciclovir in preventing cytomegalovirus (CMV) disease has not been documented in liver transplant recipients. We sought to compare the efficacy of pre-emptive oral ganciclovir with that of i.v. ganciclovir for the prevention of CMV disease after liver transplantation, and to determine whether withholding prophylaxis in the absence of CMV antigenemia, reliably identified patients in whom no prophylaxis was necessary. METHODS: Surveillance cultures for CMV pp65 antigenemia were performed in all patients at weeks 2, 4, 6, 8, 12, and 16. Patients with CMV antigenemia were randomized into two study groups. The experimental group received oral ganciclovir for 6 weeks (2 g t.i.d. for 2 weeks, then 1 g t.i.d. for 4 weeks), and the control group received i.v. ganciclovir (5 mg/kg q 12 hr) for 7 days. RESULTS: Of 72 consecutive liver transplant recipients studied, CMV antigenemia occurred in 31% (22 of 72). Twenty-two patients with asymptomatic antigenemia were randomized to two study groups. CMV disease (viral syndrome) occurred in 9% (1 of 11) of the patients in the i.v. ganciclovir group and in 0% (0 of 11) of the patients in the oral ganciclovir group. None of the study patients developed tissue invasive CMV disease. The median reduction in antigenemia level with oral ganciclovir was 55% at week 1, and 100% at week 2. Overall, 64% of the patients by week 1, 93% by week 2, and 100% by week 4 had antigenemia levels below the baseline after oral ganciclovir. Of 50 patients without CMV antigenemia, none developed CMV disease. CONCLUSIONS: Pre-emptive prophylaxis based on CMV antigenemia can effectively target the patients for CMV prophylaxis; 69% of the patients never received antiviral prophylaxis and did not develop CMV disease. Antiviral therapy instituted upon detection of antigenemia prevented tissue invasive CMV in both ganciclovir groups. Pre-emptively administered oral ganciclovir was effective as prophylaxis for CMV disease after liver transplantation.     

Prevention of Cytomegalovirus Disease in Renal Transplantation: Single-Center Experience

Cytomegalovirus (CMV) infection and CMV disease remain important issues in renal transplantation. Incidence depends on individual patient risk. There are different possible strategies for CMV prophylaxis. In our center CMV prevention includes prophylaxis with low-dose valganciclovir for all high-risk recipients; for the remaining patients, valganciclovir is only prescribed when there is evidence of CMV replication. All recipients are monitored for viral replication. We evaluated the results of this preventive strategy in all 135 patients who underwent transplantation between 2006 and 2007 in our center. Average follow-up time was 16 months (6-30 months). Fifty-one recipients (38%) received CMV prophylaxis. The median duration of prophylaxis was 84 days. In 37% of the recipients (50 patients) CMV antigenemia became positive, and were given therapeutic doses of valganciclovir. Of these patients, 32% were high-risk recipients undergoing prophylaxis. CMV infection rate was 40% in the group not receiving prophylaxis. No association was observed between CMV infection and prophylaxis duration. However, 50% of patients who suspended prophylaxis before completion of the first 3 months became infected. There were 3 cases of CMV disease (2.2%). Leukopenia was seen in 34% of patients receiving prophylaxis. Valganciclovir prophylaxis for high-risk patients seems to be effective and safe among subjects who complete the full duration of treatment. Despite CMV-positive antigenemia in 40% of patients not undergoing prophylaxis, pre-emptive therapy with valganciclovir was effective to prevent CMV disease, but close monitoring is essential for disease prevention.     

The impact of pretransplant cytomegalovirus infection on acute renal allograft rejection

BACKGROUND: The role of cytomegalovirus (CMV) infection in renal allograft rejection remains controversial; moreover, there are few studies on pretransplant infections. This study sought to investigate whether pretransplant CMV infections had negative effects on acute rejection episodes (ARE) and to evaluate the effect of preemptive treatment. METHODS: This retrospective single-center study of 416 transplant recipients from October 1, 2000 to September 1, 2003 had CMV infections diagnosed by CMV antigenemia tests. The incidences of ARE were compared between CMV-infected and noninfected groups. Risk factors for ARE were analyzed. Based on preemptive treatment, pretransplant CMV-infected recipients were divided into ganciclovir-treated and nontreated groups and the incidence of ARE was compared between the two groups. RESULTS: One hundred eighty four recipients had CMV infections pretransplant; the infection rate was 44.2%. Fifty five recipients had ARE among the pretransplant CMV-positive group, which was significantly higher than that in the noninfected group (29.9% vs 19.5%, P = .014). But the rejection subgroups and renal function recovery had no significant differences. While the presence of pretransplant infection was an independent predictor of ARE (RR = 1.807), severity showed no significant impact on ARE. Among 184 pretransplant CMV infection recipients, the incidences of ARE were 14.3% and 18.0% in ganciclovir-treated versus nontreated patients, respectively (P = .650). CONCLUSIONS: Pretransplant CMV-positive recipients were at greater risk of ARE. Pretransplant CMV infection was an independent risk factor for ARE. Preemptive antiviral treatment did not show protective effects against ARE related to CMV infection-mediated immunological injuries.     

The value of pre-emptive therapy for cytomegalovirus after liver transplantation

Background

Cytomegalovirus (CMV) infections are among the most common infections following liver transplantation. The main preventive methods for CMV infections are universal prophylaxis and pre-emptive therapy. In our study, we adopted a pre-emptive strategy in a higth-risk group of donor CMV-positive (D+)/recipient CMV-negative (R−) casses. We investigated whether this strategy was safe and effective to prevent CMV disease.

Methods

One hundred fifty-nine liver transplantation recipients who underwent over a 15-year period were retrospectively analyzed after follow-up for at least 6 months (mean, 63 months). Weekly quantitative polymerase chain reaction (PCR) measurements were performed to detect viral DNA. No CMV drug prophylaxis was given: antiviral CMV therapy was initiated when the PCR for CMV-DNA was >400 copies/mL.

Results

Fifty-one of 159 liver transplant recipients enrolled in the study received antiviral therapy. High-risk patients (D+/R−) developed CMV infections significantly more often than D−/R− serostatus (P = .005). CMV disease was diagnosed in 12% of CMV-positive patients. Independent of serostatus in 14 cases (27.5%) virological recurrence of CMV infection occurred after primary treatment. Survival analysis showed no significant difference between patients with versus without CMV infection (P = .950). No relationship could be found between transplant rejection and CMV infection (P = .349).

Conclusion

Our results showed that a pre-emptive strategy to prevent CMV disease was possible, even among the serological high-risk group. Only 12% of cases with CMV infection went on to manifest CMV disease with organ involvement. Survival curves were similar among patients with versus without CMV infections.     

Cytomegalovirus infection and graft rejection in renal transplantation

BACKGROUND: Cytomegalovirus (CMV) infection and CMV disease have been associated with acute and chronic graft rejection. The introduction of the sensitive CMV antigenemia pp65 assay for detection of CMV infection allowed us to study the time course of CMV infection and acute rejection and the long-term outcome in renal transplant recipients with and without a CMV risk constellation. METHODS: Prospective single center study including 48 renal transplant recipients at risk for CMV infection (donor and/or recipient CMV seropositive) and a control group of 36 CMV seronegative recipients of CMV seronegative kidney donors. Evidence of CMV infection was monitored by the CMV antigenemia pp65 assay every 1 to 2 weeks and compared with the occurrence of acute rejection in the posttransplant period and graft function at 5 years. RESULTS: CMV infection developed in 83% (40/48) of patients of the CMV risk group within 4 months posttransplant. A total of 18 of patients experienced an acute rejection episode (control group 16/36; P=0.65). In 12/18 CMV infection followed rejection and in three patients antigenemia preceded the diagnosis of rejection. In three patients CMV antigenemia remained negative. Five-year follow up: Patient survival (44/48 vs. 31/36; P=0.48), graft survival (38/48 vs. 27/36; P=0.79), number of patients with at least one acute rejection episode: CMV risk group: 42.1%, control group 51% (P=0.46), serum creatinine: CMV risk group:130 +/- 66 micromol/iter, control group: 126 +/- 37 micromol/ liter (P=0.56), proteinuria: CMV risk group: 0.02 +/- 0.02 g/mmol creatinine, control group: 0.02 +/- 0.02 g/mmol creatinine (P=1.0). CONCLUSION: CMV infection within 4 months posttransplant, as defined by a positive antigenemia assay was not found to be a risk factor for acute graft rejection or chronic graft dysfunction at 5 years.     

Cytomegalovirus infection with multiple colonic perforations in a renal transplant recipient

Cytomegalovirus (CMV) continues to be potentially the most important pathogen affecting organ transplant recipients. Severe gastrointestinal complications have been reported to occur in about 10% of renal transplant recipients, sometimes with dramatic presentations. We report the case of a 57-year-old CMV-seropositive woman with end-stage renal failure who developed CMV-related colonic multiple perforation 30 days after cadaveric CMV-positive renal transplantation. CMV pp65 antigenemia test and CMV-PCR had always been negative on all the weekly controls routinely performed in the postoperative period. Only after the sudden onset of this complication did the antigenemia and PCR become positive. The relationship between infection and perforation has been established beyond any doubt, as the histology of the resected colonic segment revealed florid CMV infection with evidence of typical inclusions in both macrophages and endothelial cells. Colonic perforations are often fatal in transplant recipients because of inability to contain the perforation, and only a rapid diagnosis and an aggressive surgical treatment can improve the prognosis.     

Monitoring of human cytomegalovirus infections in heart transplant recipients by pp65 antigenemia

BACKGROUND: Rapid diagnostic techniques offer the opportunity of early diagnosis of human cytomegalovirus (CMV) infection in immunocompromized patients at risk of developing CMV disease and syndrome. The use of CMV pp65 antigenemia as a predictor of CMV syndrome and disease in heart transplant recipient after induction therapy was studied retrospectively. METHODS: One hundred and nineteen consecutive heart transplant recipients treated with induction therapy who survived more then 14 d were monitored for CMV infection. Ninety-four recipients were seropositive for CMV. Twenty-five recipients were seronegative for CMV and received grafts from seropositive donors. Pre-emptive therapy was used in seropositive patients when CMV pp65 antigenemia was greater than 50 antigen-positive cells per 2 x 10(5) peripheral blood leukocytes (PBL); prophylactic therapy was done only in seronegative recipient matched with seropositive donor. RESULTS: High-level CMV pp65 antigenemia (50 antigen-positive cells 2 x 10(5) PBL) occurred in 34% (41 of 119) of patients at a median of 44 d following transplantation. In seropositive recipients, 16% (15 of 94) of patients developed CMV invasive disease or syndrome, and in seronegative recipients 20% (5 of 25) of patients developed CMV disease or syndrome. Sixty-six per cent (62 of 94) of CMV seropositive patients were identified as not requiring pre-emptive therapy. In seropositive and seronegative recipients, the sensibility and negative predictive value of the cut-off level of 50 antigen positive cell for CMV disease and syndrome was 100%. The specificity was 79% and positive predictive value was 49%. CONCLUSION: Because of the excellent sensibility and negative predictive value of the cut-off level of 50 antigen positive cell per 2 x 10(5) PBL, application of pre-emptive therapy guided by high level of CMV pp65 antigenemia in the context of induction therapy allow to omit antiviral therapy in many at risk patients. In the context of pre-emptive and prophylactic therapy, the cut-off level of 50 antigen positive cell do not allow to predict with accuracy the development of CMV disease or syndrome.     

Clinical usefulness of plasma quantitative polymerase chain reaction assay: diagnosis of cytomegalovirus infection in kidney transplant recipients

Background

Preemptive therapy is used to prevent cytomegalovirus (CMV) disease in transplant recipients. The CMV antigenemia assay, which has been commonly used as a predictive marker for preemptive therapy, requires intensive labor and immediate processing. We compared the cutoff value of plasma CMV polymerase chain reaction (PCR) with CMV antigenemia in kidney transplant recipients.

Methods

We compared two diagnostic methods for CMV infection in kidney transplant recipients: quantitative PCR (qPCR) versus antigenemia. We evaluated the optimal cutoff value of plasma CMV qPCR by using receiver-operating characteristic curves for specific antigenemia values. All kidney transplant recipients from January 2004 to January 2005 were enrolled and followed with CMV antigenemia and plasma CMV qPCR.

Results

The analyses were performed on 899 samples collected from 111 patients in the early posttransplant period, matching 84.1% of patients for the results of CMV antigenemia and plasma CMV qPCR. For patients with symptomatic CMV infection and disease, who showed ≥25 positive cells in the antigenemia assay, the cutoff value for qPCR was 17.8 copies/μL with a sensitivity of 97.1%, a specificity of 89.1%, and a positive predictive value of 26.6%.

Conclusions

Diagnostic assays for CMV such as CMV antigenemia and quantitative plasma PCR, showed similar diagnostic values. They are the methods of choice for the diagnosis and monitoring of active CMV infection after kidney transplantation. However, because of the relatively low positive predictive value of qPCR, this test may lead to unnecessary preemptive treatment in kidney transplant recipients.     

Cytomegalovirus infection after renal transplantation: selective prophylaxis and treatment

We have reviewed our experience in selective cytomegalovirus (CMV) infection prophylaxis and treatment in our renal transplant population. Between 1996 and 2001, 263 cadaveric renal transplant recipients had at least 6 months follow up. Immunosuppression was based on cyclosporine Neoral (n=108) or tacrolimus (n=155). CMV infection prophylaxis (oral acyclovir or gancyclovir at half usual doses) was only prescribed in recipients receiving a CMV positive ve kidney and in recipients treated with OKT3. CMV infection was diagnosed by a positive pp65 antigenemia upon appearance of CMV-related symptoms, leading to specific treatment (IV ganciclovir) only if symptoms were intense or there was visceral involvement. Thus, no preemptive treatment or programmed or periodic antigenemia was performed in any case. Nineteen episodes of symptomatic CMV infection were diagnosed (prevalence 7.2%). The frequency was similar for all immunosuppressive regimens. Only 9 of 19 (47%) of patients were given IV ganciclovir; the others were not treated. All patients survived without apparent complications, relapses, or recurrences. No oral gancyclovir was delivered after IV treatment. Our CMV prophylaxis protocol was limited to high-risk patients, using lower gancyclovir dosages than those usually advocated. It does not include programmed or scheduled search for CMV antigenemia in asymptomatic renal transplant patients. Despite these factors, our CMV infection rate and severity were similar to those reported with more aggressive protocols, with extended prophylaxis, preemptive therapy, or intense surveillance.     

Human herpesvirus-6 in liver transplant recipients: role in pathogenesis of fungal infections, neurologic complications, and outcome

BACKGROUND: The clinical impact and relevance of human herpesvirus-6 (HHV-6) infection in liver transplant recipients, has not been fully discerned. METHODS: A prospective study of 80 consecutive liver transplant recipients was performed using surveillance cultures for HHV-6 at weeks 2, 3, 4, and 6 after transplantation. Viral isolation was used for the detection of HHV-6. RESULTS: HHV-6 infection occurred in 39% (31 of 80) of the patients. Patients with HHV-6 infection were more likely to have hepatocellular carcinoma as underlying liver disease (P=.09). Mental status changes of unidentifiable etiology were significantly more likely to occur in patients with HHV-6 compared with those without (26%, 9 of 31 vs. 6%, 3 of 49, P=.008). HHV-6 infection was an independent predictor of invasive fungal infections (odds ratio 8.3, 95% confidence interval, 1.2-58.0, P=.03). A significant association between HHV-6 infection and CMV infection after transplantation, CMV recipient and donor serostatus, rejection, or fever of unknown origin, could not be documented. Mortality at last follow-up in patients with HHV-6 infection (29%, 9 of 31) was significantly greater than those without HHV-6 (6%, 3 of 49, P=.008). CONCLUSIONS: Central nervous system complications of unknown etiology after liver transplantation may be related to HHV-6 infection. HHV-6 viremia was an independently significant predictor of invasive fungal infections and was associated with late mortality in liver transplantation recipients.     

Insidious course of cytomegalovirus infection in hand transplant recipient: case report, diagnostics, and treatment

Cytomegalovirus (CMV) infection is common in solid organ and composite tissue transplant recipients and so becomes an ever more important issue for clinicians of every specialty. In this article we describe a case of CMV infection in a hand transplant recipient, which led to an episode of acute rejection early posttransplantation that was unresponsive to antiviral therapy. Our observations support the guidelines of matching CMV-positive donors with CMV-positive recipients only; however, the possible consequences related to CMV disease make a strong point to advocate the use of CMV prophylaxis in all hand transplant recipients.